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Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity

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Abstract

Rationale

Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood.

Objectives

The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli.

Methods

We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design.

Results

Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula.

Conclusions

These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity.

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Conflicts of interest

Dr. McCabe has acted as a consultant to P1Vital, Givaudan, GWpharma, the British Broadcasting Company (BBC) and Channel 4. Professor Harmer is a company director of Oxford Psychologists and has acted as a consultant to Servier, GlaxoSmithKline, Astra Zeneca, Johnson & Johnson, Roche, Lundbeck and P1Vital. Professor Cowen is a member of an advisory board for Lundbeck. Elizabeth Murray, Sietske Brouwer and Rob McCutcheon report no biomedical financial interests or potential conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry, Warneford Hospital, University of Oxford, Neuroscience Building, Oxford, OX3 7JX, UK

    Elizabeth Murray, Sietske Brouwer, Rob McCutcheon, Catherine J. Harmer & Philip J. Cowen

  2. School of Psychology and Clinical Language Sciences, University of Reading, Reading, RG6 6AL, UK

    Ciara McCabe

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  1. Elizabeth Murray
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  3. Rob McCutcheon
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  4. Catherine J. Harmer
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  5. Philip J. Cowen
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  6. Ciara McCabe
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Correspondence to Ciara McCabe.

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Murray, E., Brouwer, S., McCutcheon, R. et al. Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity. Psychopharmacology 231, 4323–4335 (2014). https://doi.org/10.1007/s00213-014-3573-7

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